Osteoarthritis (OA) is the most prevalent joint disease, causing joint pain and dysfunction. OA is also associated with substantial co-morbidity and reduces life expectancy. Pharmacologic therapy is limited to symptom modification and disease-modifying therapies are currently not available. Furthermore, even symptom-modifying therapies are limited in efficacy and can be associated with adverse reactions. This proposal is based on extensive prior work that identified N-acetylglucosamine (GlcNAc) as an agent with potential for both, symptom and disease modification in OA. GlcNAc has a spectrum of desirable activities in cell culture models and anti-inflammatory, analgesic and OA disease-modifying activity in animal models. The long-term goal of is to determine efficacy of repeated intraarticular injections of GlcNAc in the treatment of OA. Towards this goal we recently established safety of single intraarticular injections of up to 100mM GlcNAc in patients with knee OA. The next step and goal of the proposed STTR Phase I study is to establish safety of repetitive intraarticular injections of GlcNAc. Patients with knee OA will receive one injection of GlcNAc per week for three consecutive weeks. An escalating dosing scheme will be used including 1,10 and 100mM GlcNAc. Patients will be monitored for local and systemic adverse reactions. [unreadable] [unreadable] [unreadable]